In patients undergoing radial forearm free flap harvest, such as for the purpose of head and neck region reconstruction, approximately 23-55% of the patients experience donor site skin graft failure that results in delayed wound healing. Treatment usually requires prolonged immobilization of the forearm and hand. Such treatment adversely affects daily activities and, in the long term, can impair range of motion in the hand. In addition, some patients eventually require further surgery to reconstruct the nonhealing forearm donor site. (See, for example, Chang et al., Microsurgery 17:136-140 (1996)).
In view of the above, it would be desirable to provide a method of promoting healing of a radial forearm free flap site that does not require prolonged immobilization of the forearm and hand. It also would be desirable to provide a method of promoting healing of a radial forearm free flap site that does not require further surgery to reconstruct the nonhealing donor site. Such a method also would have utility in the treatment of other nonhealing wounds.
A fistula is an abnormal communication between two epithelialized surfaces, e.g., the skin and a hollow organ. Types of fistulas include enterocutaneous, esophageal/tracheal, bronchopleural and anal fistulas. The etiology of an enterocutaneous fistula is usually iatrogenic (75-85%), i.e., following surgery, in particular alimentary tract surgery, or instrumentation, although an enterocutaneous fistula can be due to the presence of a tumor, an infection, an inflammation, ischemia or exposure to radiation. Fistulas can be classified as “high output,” if their output is greater than 500 ml over a 24 hr period, and “low output,” if drainage is less than 500 ml over a 24 hr period (Foster et al., Surg. Clin. N. Am. 76(5): 1019-1033 (1996)).
The major causes of mortality due to enterocutaneous fistulas are sepsis, electrolyte disturbance and malnutrition. Enterocutaneous fistulas result in the loss of fluid, trace elements, protein and minerals (Edmunds et al., Ann. Surg. 152: 445-471 (1960)). Reported rates of enterocutaneous fistulas range from 6.5% to 21%. There also can be considerable morbidity and, in particular, fistula effluent can result in escoriation and maceration of surrounding skin (Foster et al. (1996), supra).
The spontaneous rate of fistula closure is 60-75%. Fistulas fail to close spontaneously for a number of reasons. Nonhealing of certain enterocutaneous fistulas is associated with adjacent abscess, intestinal discontinuity, distal obstruction, poor adjacent bowel, a fistula tract that is less than 2 cm in length, radiation damage, carcinoma, enteral defects greater than 1 cm and location, such as the stomach, the lateral duodenum, the ligament of Treitz and the ileum (Berry et al., Surg. Clin. N. Am. 76(5): 1009-1017 (1996); and Edmunds et al. (1960), supra).
Current approaches to promote fistula closure can be time-consuming and considerably costly to the patient and the medical community. Although management of enterocutaneous fistulas with parenteral nutrition and suppression of gastrointestinal secretions with somatostatin analogues results in decreased fistula output, an increase in the rate of fistula closure has not been observed with such treatment. Some investigative efforts have focused on identification of nutritional constituents, which could improve mucosal healing. Not uncommonly, however, the patient faces surgical exploration with excision of the fistula tract. Furthermore, in the debilitated patient, the surgical management of a chronic non-healing fistula may be dangerous, if not impossible.
There have been numerous reports of the use of various sealants, including synthetic and biological sealants, such as the use of isobutyl-2-cyanoacrylate (Histoacryl) and fibrin to close refractory enterocutaneous fistulae (Shand et al., Gastrointest. Endoscopy 46(4): 357-358 (1997); and Cellier et al., Gastrointest. Endoscopy 44(6): 731-733 (1996)). All have met with limited success. Use of the fibrin sealant, which may stimulate local fibroplasia, may, at times, be cumbersome, requiring injection in rapid succession of human fibrinogen and thrombin, which may initiate and enhance signals required for neovasularization and wound healing (Santos et al., Hepato-Gastroentero. 44: 1085-1089 (1997)), usually onto an absorbable fabric to prevent the sealant from being flushed from the fistulous tract. Results have been best when injections are performed from the internal and external opening of the tract in the case of gastrocutaneous fistulas, requiring endoscopic intervention. This technique, therefore, is limited by the reach of the endoscope, and fistulas located more distally in the alimentary tract remain a problem. For these more distally located fistulas, there has been some limited experience with injecting sealant through a catheter advanced through the tract under fluoroscopic guidance (Santos et al. (1997), supra). However, long-term occlusion is not always achieved. In addition, inherent to the use of biological agents is the possibility of transmission of infectious agents.
In view of the above, it would be highly desirable to provide a method of promoting healing of a fistula that is minimally invasive, speeds the process of fistula closure, has the potential to avoid surgery, and provides significant cost savings through reduced hospital stay and chronic requirements for parenteral nutrition.
Therefore, it is an object of the present invention to provide a method of promoting healing of a wound or fistula in an animal. This and other objects and advantages of the present invention, as well as additional inventive features, will become apparent from the description set forth herein.